BMJ comments on new PACE trial data analysis

[jimells]

But the main message at the moment as far as the UK media is concerned has to be challenging the conclusions and recommendations that have emerged from this new analysis of the PACE trial data.

I do appreciate the difficulties of navigating treacherous political waters, especially within the context of a non-profit organization. And thank you for engaging with us on this topic. I know we're all trying to get to the same destination.

 

[Esther12]

I do appreciate the difficulties of navigating treacherous political waters, especially within the context of a non-profit organization. And thank you for engaging with us on this topic. I know we're all trying to get to the same destination.

Yeah - I'm jumping to my concerns, but also appreciate a lot of the work I see the MEA doing.

 

[Aurator]

Is the respondent Timothy M. Jordan really a doctor? His latest reply (excerpted below) is so inarticulate and defensive I have my doubts. Maybe he just feels horribly outgunned.

" Evidence-based medicine with all its faults, has much for which to be recommended. The saga of poor or absent evidence may be attributed to the awful quality of research design, manipulation of research data, conflicts of interest and political interference. It cannot be stressed enough as to the poor record of academia in maintaining standards.
Maintaining scepticism is healthy and also a key ingredient when faced with any conundrum. No amount of emotional out-pouring should be allowed to disrupt rational thought.
It is with this in mind, that I find disgraceful, your efforts to criticise and demonise. I note your conflict of interest, despite your denial to the contrary....Emotional outbursts and political posturing only serve to undermine and discredit your cause."

 

[biophile]

The first part of Timothy M. Jordan's post quoted above was OK, but then ...

It is with this in mind, that I find disgraceful, your efforts to criticise and demonise. I note your conflict of interest, despite your denial to the contrary....Emotional outbursts and political posturing only serve to undermine and discredit your cause.

Would such a comment be approved by the BMJ Raid Response moderators if the same thing was said against authors of the article in question? It appears to be in response to Sonya Chowdhury, who got a little cheeky: "Finally, a suggestion for Dr Timothy M Jordan in Canada: maybe you’d like to share your brilliant, evidence-based cure with the scientists at Stanford University who recently found right arcuate fasciculus abnormality in patients with CFS (Zeineh et al, 2014, Radiology)."

 

[Kati]

The first part of Timothy M. Jordan's post quote above was fine, but then ...



Would such a comment be approved by the BMJ Raid Response moderators if the same thing was said against authors of the article in question? It appears to be in response to Sonya Chowdhury, who got a little cheeky: "Finally, a suggestion for Dr Timothy M Jordan in Canada: maybe you’d like to share your brilliant, evidence-based cure with the scientists at Stanford University who recently found right arcuate fasciculus abnormality in patients with CFS (Zeineh et al, 2014, Radiology)."

Shame on Canada for ignoring ME for 30 years. This dr's reaction is sadly the norm here. i mentioned it before but I will mention it agian, an internist wrote down in his consultation note about me " ...as you know with a patient like her the last thing we should do is provide further testing therefore reinforcing to the patient that her illness is physical..."

 

[Snow Leopard]

One thing that I think needs to be pointed out - is that there are different models of pacing which have been shown to be similarly effective to CBT in the USA, eg the models developed by Jason et al. I think this sort of alternative is worthwhile for the likes of @charles shepherd to mention each time it is said that 'pacing' does not work.

The choice is not UK CBT or GET vs nothing, despite how it is reported in the media (or the BMJ in this case).

 

[Sean]

I therefore call on, at a minimal, the 50 experts who signed the NIH CFSAC ICC letter and aslo include Ian Lipkin, to come up with, lets say 50, bullet points about the conduct of the Wessely camp, call a press conference and take the PACE trial and the Wessely school to task.

We could really use something like this, to break the perception within the profession and also the broader community wide open and get some debate about it all going. Probably best not to concentrate on PACE alone, but make it a bit more general about the whole psychosocial approach in ME/CFS. Though PACE can be the symbol of it all.

Also might be worth waiting until the final P2P and IOM reports are done.

 

[Sasha]

Apologies if this is not clear. I was trying to explain that patients who respond to our surveys are not normally being treated as part of research studies/clinical trials. Consequently, most people who take part in our surveys have not been treated in centres where the CBT and GET research studies/clinical trials have been carried out - with a few exceptions. It may well be that this is one of the main reasons for the vast discrepancy between the results in these patient surveys and the results from the RCTsthat are carried out in specialist referral centres here in the UK.

PACE excluded severe patients, which may be one of the reasons. Anyone unable to cope with repeated trips to the NHS unit to take part in group CBT if they were randomised to that condition wouldn't have been enrolled.

 

[user9876]

Yes, we also do clinical assessment work at home where this is appropriate with MEA funded research studies.

For example, we are collecting blood samples through home visits from a cohort of people with severe ME/CFS for the ME Biobank that we fund at the Royal Free Hospital in London.

But it's just not possible to do this in research that involves an exercise challenge where you are wanting to do cardiopulmonary testing using quite complex equipment.

I would think it would be a good idea to do some baseline testing with samples taken from home visits after people have rested. Then do further testing prior and at regular periods after the exercise challenge. The problem is if you are measuring a dynamic system and the act of measurement reflects on the system. I this case getting into the clinical environment for blood tests could effect patients who undergo the exercise test.

 

[Roy S]

This is part of what Sonya Chowdhury wrote in the BMJ rapid responses. I think strong statements like these need to be continually made.

"We have been astounded by the perpetuation of inaccurate and negative stereotypes in some of the press headlines about this research. This leads to ill-informed, judgemental and harmful treatment of people with this debilitating condition, many of whom are among the most neglected in society."

 

[charles shepherd]

We could really use something like this, to break the perception within the profession and also the broader community wide open and get some debate about it all going. Probably best not to concentrate on PACE alone, but make it a bit more general about the whole psychosocial approach in ME/CFS. Though PACE can be the symbol of it all.

Also might be worth waiting until the final P2P and IOM reports are done.

Reply

Have you seen that I have already written to Prof Mark VanNess to see if we can get this moving? Letter is already posted elsewhere in this discussion. I have been involved in organising this type of joint letter in the past - it can be done but getting up to 50 international 'ME/CFS experts' to agree on the final draft can be a bit like herding cats!

 

[charles shepherd]

BMJ rapid responses so far:

http://www.bmj.com/content/350/bmj.h227/rapid-responses

This debate on the BMJ website, where most doctors are going to look if they want to follow up reaction to this paper, could do with a few more good letters that are making valid and constructive points.

 

[Jonathan Edwards]

BMJ rapid responses so far:

http://www.bmj.com/content/350/bmj.h227/rapid-responses

This debate on the BMJ website, where most doctors are going to look if they want to follow up reaction to this paper, could do with a few more good letters that are making valid and constructive points.

I have tried to upload something. I guess it will take time to appear.

A couple of further thoughts.

I would be against spending resources on anything similar to PACE re other exercise protocols. The basic format of an unblinded trial is uninterpretable. What is needed is a more subtle approach. I do not know exactly what but I suspect there are ways of mitigating the placebo issue.

A huge problem that I see with PACE is that anybody who is intelligent enough to realise that either CBT or GET might be distressing in their case would not have volunteered. Thus it may be that 80% of potential volunteers were put off even before starting - leaving a decidedly biased cohort to enter, presumably unaware of having PEM if they did have it. The number of sources of bias in this study seems almost endless. The trouble is it is no good saying oh well this is the best we can do so let's do it. If it is valueless then there is no point.

 

[Sasha]

I have tried to upload something. I guess it will take time to appear.

A couple of further thoughts.

I would be against spending resources on anything similar to PACE re other exercise protocols. The basic format of an unblinded trial is uninterpretable. What is needed is a more subtle approach. I do not know exactly what but I suspect there are ways of mitigating the placebo issue.

A huge problem that I see with PACE is that anybody who is intelligent enough to realise that either CBT or GET might be distressing in their case would not have volunteered. Thus it may be that 80% of potential volunteers were put off even before starting - leaving a decidedly biased cohort to enter, presumably unaware of having PEM if they did have it. The number of sources of bias in this study seems almost endless. The trouble is it is no good saying oh well this is the best we can do so let's do it. If it is valueless then there is no point.

Thanks for responding! Looking forward to seeing your thoughts published.

I was invited to take part in PACE but was simultaneously discouraged (I thought) by the recruiters. I interpreted that as a humane act on their part. I couldn't have coped with repeated hospital visits and was so sick I wanted the best treatment, not the one I was randomised to.

I asked if I could see a copy of the trial protocol and was told I couldn't. I still don't understand why not. I don't see how one can give genuine informed consent if one is unaware of not only the personal risk involved with the interventions, but also of whether the trial is a badly designed pile of **** that doesn't deserve that you risk your health for it.

As we've seen, the authors have refused multiple FOI requests for data from patients and those who represent them. If I'd been a health-risking patient in that trial, I'd be disgusted that my (aggregated) data weren't being made available to other patients and their clinicians. I'm disgusted anyway.

 

[Sasha]

A huge problem that I see with PACE is that anybody who is intelligent enough to realise that either CBT or GET might be distressing in their case would not have volunteered. Thus it may be that 80% of potential volunteers were put off even before starting - leaving a decidedly biased cohort to enter, presumably unaware of having PEM if they did have it.

I recall reading that the original entry criteria for enrolment were relatively tight and would have been ME cases but there were problems with recruitment and that the criteria were changed to the weak Oxford 'CFS' criteria.

Does anyone recall if that is true? I thought that Peter White had said in print that these are not ME patients - is that also true?

 

[Wildcat]

.
Re Peter White on PACE not being a 'CFS/ME' study: I think there is more on that but can't find it at present.



http://www.investinme.org/Article42...oper to undated letter by White to Horton.htm

Initial response by Professor Malcolm Hooper to an undated letter sent by Professor Peter White to Dr Richard Horton, Editor-in-Chief of The Lancet

18th May 2011


On 17th May 2011 Zoe Mullan, Senior Editor at The Lancet, sent an email to Professor Hooper in response to the complaint he submitted about the PACE Trial article published online by The Lancet on 18th February 2011 and subsequently in the journal on 5th March 2011. In her email, Zoe Mullan wrote: “We asked the authors of the PACE trial to respond to your concerns, which they have duly done. Your complaint and their response were discussed at the highest management level and this group of executive editors was fully satisfied that there were no grounds whatsoever on which to take further action. We attach the response provided to us here. From an editorial perspective, the case is now closed”.

The undated response to Professor Hooper’s complaint by Professors White, Sharpe and Chalder that was sent to Dr Richard Horton (Editor-in-Chief of The Lancet) on behalf of all the co-authors will, in the interests of openness and transparency, be placed in the public domain and will be fully addressed in due course, as will Professor Hooper’s concerns over what he believes is the failure of The Lancet’s editorial process in this instance, but there is one point in Professor White’s letter that is of particular importance, so it is addressed in this initial response.


‘In their letter, Peter White et al state: “The PACE trial paper refers to chronic fatigue syndrome (CFS) which is operationally defined; it does not purport to be studying CFS/ME”.

The sentence continues by stating that the PACE Trial studied: “CFS defined simply as a principal complaint of fatigue that is disabling, having lasted six months, with no alternative medical explanation (Oxford criteria)”…… ‘
.

 

[charles shepherd]

I have tried to upload something. I guess it will take time to appear.

A couple of further thoughts.

I would be against spending resources on anything similar to PACE re other exercise protocols. The basic format of an unblinded trial is uninterpretable. What is needed is a more subtle approach. I do not know exactly what but I suspect there are ways of mitigating the placebo issue.

A huge problem that I see with PACE is that anybody who is intelligent enough to realise that either CBT or GET might be distressing in their case would not have volunteered. Thus it may be that 80% of potential volunteers were put off even before starting - leaving a decidedly biased cohort to enter, presumably unaware of having PEM if they did have it. The number of sources of bias in this study seems almost endless. The trouble is it is no good saying oh well this is the best we can do so let's do it. If it is valueless then there is no point.

Jonathan - BMJ rapid responses are all moderated before they appear. And I suspect the moderater may be having a day off today!

I agree that there are huge problems in designing some form of trial that is going to produce a meaningful assessment of the safety and efficacy of pacing - however we decide to define it

But unless we do something to test out the theory of pacing we are just going to be responding to yet more studies - and there are more in the pipeline - which claim that GET is the best form of activity/energy management for ME/CFS

 

[Kati]

Jonathan - BMJ rapid responses are all moderated before they appear. And I suspect the moderater may be having a day off today!

I agree that there are huge problems in designing some form of trial that is going to produce a meaningful assessment of the safety and efficacy of pacing - however we decide to define it

But unless we do something to test out the theory of pacing we are just going to be responding to yet more studies - and there are more in the pipeline - which claim that GET is the best form of activity/energy management for ME/CFS

I would like to thank both @charles shepherd and @Jonathan Edwards for mingling and participating in the forum over here. It is absolutely refreshing to see both of your involvement in the community.

 

[Wildcat]

.
Charles Shepherd wrote: "But unless we do something to test out the theory of pacing we are just going to be responding to yet more studies - and there are more in the pipeline - which claim that GET is the best form of activity/energy management for ME/CFS"


Surely there is enough research already existing to refute GET as treatment for ME. Any pacing trial would require pacing to be tested over a long period of time. Who would fund a pacing trial? And is a pacing trial really the research priority at this point?

Are we prepared to hold our collective breath for yet another decade, hoping that a pacing study would validate pacing? The decades are slipping by.

.

 

[Kati]

.
Charles Shepherd wrote: "But unless we do something to test out the theory of pacing we are just going to be responding to yet more studies - and there are more in the pipeline - which claim that GET is the best form of activity/energy management for ME/CFS"


Surely there is enough research already existing to refute GET as treatment for ME. Any pacing trial would require pacing to be tested over a long period of time. Who would fund a pacing trial? And is a pacing trial really the research priority at this point?

Are we prepared to hold our collective breath for yet another decade, hoping that a pacing study would validate pacing? The decades are slipping by.

.

Indeed a pacing trial would be similar in studying the natural history of ME which is not what is needed here. Pacing is not a treatment, it is a mere lifestyle waiting for meaningful treatment.